Highlights d Stool butyrate levels are reduced in patients with RA compared to healthy controls d Supplementation with butyrate suppresses arthritis severity in a mouse model d Suppression of arthritis by butyrate supplementation depends upon AhR + Bregs d Butyrate increases serotonin-derived 5-HIAA, which directly activates AhR + Bregs

BACKGROUND. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program has proven to be a significant resource in US neuroendocrine tumor (NET) epidemiology. Norway also holds a robust and detailed cancer registry: the Norwegian Registry of Cancer (NRC). METHODS. SEER NET data were compared with corresponding NRC data in the time period 1993 to 2004 to determine whether there are differences in NET epidemiology between Norway and the United States. RESULTS. The SEER and NRC reported 17,312 and 2030 NETs, respectively. The overall Caucasian SEER NET incidence was 4.44, compared with 3.24 in the NRC. In the SEER white subset, bronchopulmonary NETs were the most common (incidence = 1.42; 32% of all NETs), compared with small intestinal NETs in the NRC (0.81; 26%). A marked increase in SEER NET incidence (37%‐40%) was observed in the period 2000 to 2004, compared with 1993 to 1997; an even more pronounced increase (72%) was seen in the NRC. African Americans exhibited a remarkably high overall NET incidence of 6.50; furthermore, among African Americans, rectal NETs were most common (1.65; 27%). Small intestinal NET incidence was ∼30% higher in men compared with women in all populations. The highest 5‐year survival rates were for rectal NETs (74%‐88%) in both databases, whereas prostatic NETs had the worst outcome (0%‐23%). At diagnosis, NETs were localized in 27% to 46% of patients. CONCLUSIONS. NET incidence in the US Caucasian population and in Norway is similar, but considerably higher (∼50%) among African Americans. NETs have been regarded as indolent tumors; however, the 5‐year survival is only ∼55%. Cancer 2008. © 2008 American Cancer Society.

Macrophages are integral to the pathogenesis of atherosclerosis, but the contribution of distinct macrophage subsets to disease remains poorly defined. Using single cell technologies and conditional ablation via a LysMCre+Clec4a2flox/DTR mouse strain, we demonstrate that the expression of the C-type lectin receptor CLEC4A2 is a distinguishing feature of vascular resident macrophages endowed with athero-protective properties. Through genetic deletion and competitive bone marrow chimera experiments, we identify CLEC4A2 as an intrinsic regulator of macrophage tissue adaptation by promoting a bias in monocyte-to-macrophage in situ differentiation towards colony stimulating factor 1 (CSF1) in vascular health and disease. During atherogenesis, CLEC4A2 deficiency results in loss of resident vascular macrophages and their homeostatic properties causing dysfunctional cholesterol metabolism and enhanced toll-like receptor triggering, exacerbating disease. Our study demonstrates that CLEC4A2 licenses monocytes to join the vascular resident macrophage pool, and that CLEC4A2-mediated macrophage homeostasis is critical to combat cardiovascular disease.

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